Abstract
Hypoxia-inducible factor 3 subunit alpha (HIF3A) has been implicated in various types of cancers, while its precise role in the lung adenocarcinoma remains unclear. Our study aimed to investigate the roles of HIF3A in lung adenocarcinoma and its regulation by DNA methylation. We utilized bioinformatic tools, including UALCAN and KMPlot, to analyze the relationship between HIF3A expression, DNA methylation, and patient survival rate in lung adenocarcinoma. We also used siRNA-mediated knockdown of HIF3A and DNA-methyltransferase 1 (DNMT1), as well as the treatment of DNA methylation inhibitor 5-Azacytidine, in A549 and H1299 lung adenocarcinoma cell lines. qPCR, MTT, and cell counting assays were performed to evaluate the mRNA expression and cell viability. The bioinformatic analysis revealed that HIF3A expression was downregulated and its methylation was upregulated in lung tumor tissues. Additionally, Kaplan–Meier analysis indicated a correlation between low HIF3A expression and patient poor survival rate. We found that DNMT1 regulated HIF3A methylation. Knockdown of HIF3A promoted cancer cell proliferation. These data suggest that downregulation of HIF3A promotes tumor cell proliferation, and support that HIF3A methylation may serve as a prognostic factor for lung adenocarcinoma.
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The raw data supporting the conclusions of this article will be made available on request to the corresponding author by email, as requested by our department.
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The study was supported by Fuzhou Science and Technology Bureau (AFZ2019S040076).
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Data curation: Qin Shi, Xiuxia Zheng, Ying Hu, Zhan Zhou, Minshan Fang and Xinhui Huang; Project administration: Qin Shi; Supervision: Qin Shi; Writing—original draft: Qin Shi, Xiuxia Zheng, Ying Hu, Zhan Zhou, Minshan Fang and Xinhui Huang; Writing—review and editing: Qin Shi, Xiuxia Zheng, Ying Hu, Zhan Zhou, Minshan Fang and Xinhui Huang.
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Communicated by: Ewa Ziętkiewicz
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Shi, Q., Zheng, X., Hu, Y. et al. Methylation of hypoxia-inducible factor 3 subunit alpha contributes to poor prognosis in lung adenocarcinoma. J Appl Genetics 64, 769–777 (2023). https://doi.org/10.1007/s13353-023-00784-6
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DOI: https://doi.org/10.1007/s13353-023-00784-6